Abstract Objective: Cigarette smoking is an established risk factor for bladder cancer. Recent research suggests smoking-related risk has increased in the United States, in spite of decreased prevalence of smoking (JNCI 101:1553-61, 2009; JAMA 306:737-45, 2011). Hypothesized reasons for this temporal pattern include changes in how deeply smokers inhale and changes in cigarette composition, which may be related. We examined associations between smoking status and bladder cancer risk during three successive intervals between 1987 and 1996 to investigate whether level of risk had changed in our study population. To gain insight into possible effects of changing smoking habits we also evaluated impact on estimated associations of intensity and duration of smoking. Methods: We examined the association between smoking and bladder cancer risk in a population-based case-control study conducted in Los Angeles within three separate intervals defined by year of diagnosis: 1987-1989, 1990- 1992, and 1993-1996. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI) using conditional logistic regression. Cases and controls were matched on age, gender, race, and neighborhood. Further analyses were adjusted for pack years of smoking, education, and use of non-steroidal anti-inflammatory drugs (NSAIDs). Results: There were 569 cases and 553 controls in the 1987-1989 interval, 461 cases and 426 controls in 1990-1992, and 641 cases and 607 controls in 1992-1996. In each interval smoking was associated with bladder cancer risk. Compared with never smokers, OR estimates for former smokers were 1.79 [95%CI=1.30-2.48], 1.38 [95%CI=0.95-1.99], and 1.93 [95%CI=1.42-2.62] for the successive intervals. For current smokers, corresponding estimates were 3.18 [95%CI=2.29-4.4], 3.90 [95%CI=2.64-5.77], and 4.75 [95%CI=3.37-6.7]. When males and females were considered separately, these estimates were also greater in later intervals. In 1992-1996, current male smokers were 4.45 (95%CI=3.03-6.56) times as likely and current female smokers were 5.95 (95%CI=2.78-12.71) times as likely to have bladder cancer; these associations were weaker in 1987-1989: 2.95 (95%CI=2.01-4.35) and 3.75 (95%CI=2.03-6.92). After adjusting for pack years, all odds ratio estimates for current smokers were attenuated, 0.83 [95%CI=1.22-2.75], 1.86[95%CI=1.13-3.06], 2.4 [95%CI=1.54-3.75] for successive intervals, while for former smokers none of the associations were statistically significant. Conclusions: Bladder cancer risk appears to have increased among both ever smokers and current smokers, although distinctions are less pronounced after accounting for pack years of smoking. Further research is needed to learn whether this pattern reflects changes in smoking behavior, formulation of cigarettes, or other factors - and to determine whether these increases have continued. Citation Format: Donna C. Dueker, Mariana C. Stern, David V. Conti, Malcolm C. Pike, Victoria K. Cortessis. Further observation of increasing strength of the smoking-bladder cancer association: The Los Angeles Bladder Cancer Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3622. doi:10.1158/1538-7445.AM2013-3622